Introduction: Histoplasmosis is a rare opportunistic, inhalation-acquired systemic mycosis caused by Histoplasma capsulatum, endemic to Southeast Asia, including Malaysia. Although classically seen in immunocompromised hosts, it is increasingly reported in immunocompetent individuals. Infection is associated with environmental exposures such as bat or bird droppings and soil disruption. Histoplasmosis is a progressive granulomatous disease that can closely mimic tuberculosis and malignancy, making diagnosis challenging. Case: An 87-year-old Malay male with a history of treated pulmonary tuberculosis presented with a 6-month history of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2 × 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate washout characteristics. Biochemical adrenal evaluation, including a short Synacthen test, confirmed primary adrenal insufficiency. Extensive microbiological and malignancy workup, including bronchoscopy, cultures, and tumor markers, was non-diagnostic. In view of clinical deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses (SUVmax right 16.7, left 13.2) with no other abnormal foci. Non-invasive fungal investigations were negative. Definitive diagnosis was established via computed tomography-guided adrenal biopsy, which demonstrated necrotizing granulomatous inflammation with intracellular yeasts, subsequently identified as H. capsulatum. The patient was treated with oral itraconazole and corticosteroid replacement, resulting in significant clinical improvement and planned interval radiological reassessment. Conclusion Disseminated histoplasmosis is a diagnostic challenge, particularly in frail elderly patients, where invasive procedures may be delayed. It can mimic tuberculosis and malignancy and may lack an identifiable exposure history. Non-invasive tests may be inconclusive, making tissue biopsy essential. Adrenal involvement may result in primary adrenal insufficiency, further complicating the clinical picture. Early consideration and timely confirmation are crucial for appropriate management.
Adrenal incidentaloma ; Lung Neoplasms

Introduction: Skeletal disease in transfusion-dependent thalassemia is commonly attributed to reduced bone mineral density and managed with anti-resorptive therapy. However, chronic iron overload can induce progressive endocrine siderosis, disrupting anabolic pathways essential for bone homeostasis. This mechanism remains under-recognized and may underlie treatment failure in severe cases. Case: We describe a 34-year-old female with transfusiondependent HbE β-thalassemia, post-splenectomy, receiving regular transfusions and iron chelation, who sustained multiple pathological fractures following a trivial fall, including bilateral supracondylar femur fractures and a distal radius fracture. She had severe systemic iron overload (ferritin 2,621 ng/mL) complicated by hepatic cirrhosis, insulin-dependent diabetes, and hypogonadotropic hypogonadism. Bone mineral density assessment demonstrated severe osteoporosis (hip T-score −5.4) despite prolonged bisphosphonate therapy, with prior vertebral compression fracture. Endocrine evaluation revealed multiaxis dysfunction, including gonadal failure and probable growth hormone deficiency, consistent with pituitary and peripheral endocrine siderosis. Conclusion This case demonstrates that skeletal fragility in transfusiondependent thalassemia reflects an endocrine-driven failure of bone formation rather than isolated loss of bone mineral density. Iron overload–induced endocrine siderosis impairs osteoblast function and suppresses anabolic signaling, leading to profound skeletal vulnerability. The progression of osteoporosis despite anti-resorptive therapy highlights the limitation of conventional approaches and supports reframing thalassemia-associated bone disease as an endocrine disorder. Severe osteoporosis should prompt systematic endocrine evaluation, with early hormonal replacement and consideration of anabolic therapy to prevent catastrophic fractures and long-term disability.
Siderosis ; Thalassemia

Introduction: Arginine vasopressin (AVP) deficiency is an uncommon but important presentation of infiltrative hypothalamic– pituitary disorders. In adults, isolated AVP deficiency with pituitary stalk thickening is diagnostically challenging, especially in the absence of systemic disease. Langerhans cell histiocytosis (LCH) is a rare cause and may precede systemic involvement by several years. Case: We report a 42-year-old male who presented in 2017 with polyuria and polydipsia, with urine output of up to 10 L/ day. AVP deficiency was confirmed by the water deprivation test, and desmopressin was initiated. Initial pituitary magnetic resonance imaging (MRI) was normal, baseline anterior pituitary hormonal evaluation was unremarkable, and contrast-enhanced computed tomography (CECT) of the thorax and abdomen showed no abnormalities. Repeat pituitary MRI 1 year later demonstrated loss of the posterior pituitary bright spot with pituitary stalk thickening. In the absence of systemic involvement, a presumptive diagnosis of lymphocytic hypophysitis was made, and pituitary biopsy was deferred due to the high procedural risk. Serial pituitary MRIs over the following years showed persistent infundibular thickening and continued absence of the posterior pituitary bright spot, without interval progression or development of additional hormonal deficiencies. The patient remained clinically stable until June 2024, when new-onset left hip pain prompted MRI, revealing a heterogeneous mass involving the femoral neck and intertrochanteric region with a pathological fracture. Histopathological examination following wide resection confirmed LCH, with negative BRAF V600 mutation. Postoperative PET scan revealed a multisystem disease involving the skeleton, lymph nodes, spine, and gastrointestinal tract, with no bone marrow involvement. He subsequently completed six cycles of intravenous methotrexate and cytarabine. Conclusion Adult-onset AVP deficiency may be the earliest manifestation of occult multisystem Langerhans cell histiocytosis. This case highlights the importance of longterm follow-up and reconsideration of the initial diagnosis when new systemic features emerge.
Histiocytosis, Langerhans-Cell

Introduction: Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of langerin-positive histiocytes. Endocrine involvement most frequently manifests as central diabetes insipidus or secondary hypothyroidism, caused by infiltration of the hypothalamic-pituitary axis. Conversely, direct infiltration of the thyroid gland leading to primary hypothyroidism is an exceptionally rare clinical entity, particularly when presenting concurrently with central disease. Case: A 21-year-old female with known right otic and multisystem LCH presented with septic shock secondary to a right ear abscess accompanied by polyuria and polydipsia. Physical examination revealed a palpable goiter. Clinical and biochemical evaluation confirmed central diabetes insipidus with associated anterior hypopituitarism (low adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone). However, concurrent thyroid function tests demonstrated overt primary hypothyroidism, evidenced by an appropriately elevated thyroid-stimulating hormone (26.19 mIU/L) and low free T4 (5.47 pmol/L), rather than the anticipated secondary hypothyroidism. Neck ultrasound showed diffuse thyroid enlargement with heterogeneous echotexture. Crucially, anti-thyroid peroxidase and anti-thyroglobulin antibodies were both negative, rendering Hashimoto’s thyroiditis highly unlikely. Although the patient declined confirmatory fine-needle aspiration, the constellation of a palpable goiter, characteristic ultrasonographic findings, negative autoimmunity, and active multisystem disease strongly supported a diagnosis of direct histiocytic infiltration of the thyroid gland. She was initiated on appropriate glucocorticoid coverage and subsequent levothyroxine replacement, alongside systemic intravenous cytarabine. Conclusion This case highlights a rare, mixed endocrine profile in multisystem LCH, demonstrating that pituitary and direct end-organ infiltration can coexist. Hypothyroidism in LCH patients with established central diabetes insipidus should not be reflexively assumed to be central in origin. A comprehensive diagnostic workup, including autoantibody screening, ultrasound, and ideally histopathological confirmation, is essential to accurately identify primary endocrine failure and guide appropriate clinical management in these complex cases.
Histiocytosis, Langerhans-Cell ; Hypothyroidism ; Pituitary Gland

Introduction: Hashimoto's thyroiditis is a common autoimmune thyroid disease; however, pulmonary involvement is a rare manifestation. Lymphocytic interstitial pneumonitis is commonly associated with autoimmune diseases, but its association with Hashimoto's thyroiditis remains poorly understood. Case: A 63-year-old male with prior diagnosis of Hashimoto's thyroiditis presented with recurrent massive pleural effusion and progressive dyspnea. He also experienced fatigue, cold intolerance, and constipation. Physical examination revealed facial puffiness, diffuse goiter, and dry skin. Thyroid function tests performed 6 months before admission confirmed overt hypothyroidism (thyroidstimulating hormone [TSH] 80.30 µIU/mL, free thyroxine 4 [FT4] 0.46 ng/dL). One month prior to admission, laboratory findings showed subclinical hypothyroidism (TSH 9.09 µIU/mL, FT4 1.42 ng/dL). Despite levothyroxine treatment TSH levels remained elevated at 21.8 µIU/mL during admission. Anti-thyroid peroxidase antibodies were positive (13.95 IU/mL). Repeated thoracentesis revealed exudative pleural effusion with lymphocytic predominance and no evidence of malignancy in cytological examination. Infectious etiologies and malignancy were ruled out. Thyroid ultrasonography demonstrated diffuse hypoechoic enlargement of the thyroid gland. Chest radiography showed massive unilateral pleural effusion, while thoracic computed tomography revealed ground-glass opacities with a reticulogranular pattern and interlobular septal thickening, accompanied by multiple thin-walled cysts, highly suggestive of lymphocytic interstitial pneumonitis. Thyroid immunohistochemical analysis was performed (CD 20, CD 3, CD 10, CD 138, Ki 67, BCL 2, BCL 6, Thyroglobulin, MUM 1, Cyclin D1), consistent with lymphocytic thyroiditis. Significant clinical and laboratory improvement was achieved after combined treatment with levothyroxine and corticosteroid. Conclusion This case underscores the importance of considering autoimmune-related lymphocytic interstitial pneumonitis in patients with Hashimoto's thyroiditis who present with unexplained recurrent pleural effusion after exclusion of more common etiologies, such as infection and malignancy. Early recognition may lead to favorable improvement.
Lung Diseases, Interstitial ; Pleural Effusion ; Thyroiditis

Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. Complications such as cystic fibrosis–related diabetes (CFRD) are well recognized. The association between CF and autoimmune thyroid disease, however, is rare and poorly understood. We report a case of CFRD complicated by Graves’ disease. Case: A 22-year-old male was diagnosed with CF at age 5, confirmed by a positive sweat chloride test. Following the diagnosis, lifelong pancreatic enzyme replacement therapy (Creon) was initiated to treat exocrine pancreatic insufficiency. In 2021, he developed type 3c diabetes, attributed to endocrine pancreatic insufficiency, and required regular basal insulin therapy. In early 2024, he developed hypokalemic periodic paralysis with proximal myopathy, despite potassium correction, and was admitted to the hospital. On admission, examination revealed a fine tremor and diffuse bilateral neck swelling. Biochemical evaluation showed thyrotoxicosis with Free T4 of 37 pmol/L and thyroid-stimulating hormone (TSH) <0.01 mIU/L. He started a tapering dose of carbimazole and propranolol. An urgent neck ultrasound showed a heterogeneous thyroid parenchyma with increased vascularity and no nodules. Elevated anti-thyroid peroxidase (anti-thyroid peroxidase, >600 IU/mL) and TSH receptor antibodies (thyrotropin receptor antibody, 2.57 IU/L) confirmed a diagnosis of Graves’ disease. During follow-ups, he had issues with compliance with the antithyroid therapy. However, the latest thyroid function test in February 2026 showed Free T4 of 20.5 pmol/L with suppressed TSH of <0.01 mIU/L. He remains clinically euthyroid throughout the follow-up. Conclusion This case highlights a rare but clinically relevant coexistence. Clinicians managing symptomatic CF patients should vigilantly screen for thyroid dysfunction to ensure early diagnosis and timely intervention. Early recognition and treatment may improve patient outcomes. Further research is needed to clarify the immunological link between CF and autoimmunity.
Cystic Fibrosis ; Graves Disease

This report describes a case of adult temporal bone Langerhans cell histiocytosis（LCH） that presented as posterior canal dehiscence syndrome（PCDS）. The patient initially presented with vertigo, tinnitus, and hearing loss. Computed tomography（CT） revealed erosive changes in the mastoid and posterior semicircular canal. After the operation, the patient's hearing and vestibular symptoms disappeared and postoperative recovery was favorable. Adult LCH is relatively rare, and this case serves as an example to discuss the clinical features and treatment options of this disease, followed by a literature review.
Humans ; Histiocytosis, Langerhans-Cell/complications* ; Semicircular Canal Dehiscence/etiology* ; Temporal Bone/pathology*

One of the main pathological features of airway inflammatory diseases is hypersecretion of airway mucus, which is manifested by goblet cell hyperplasia and mucociliary clearance dysfunction. In recent years, it has been found that the molecular structure of calcium activated chloride ion channels, transmenbrane protein 16A（TMEM16A）, is closely related to airway mucus hypersecretion.TMEM16A not only mediates ion transepithelial transport and hydration, but also participates in the regulation of mucin secretion. TMEM16A is highly expressed in airway epithelium of a variety of inflammatory diseases of upper and lower airway, such as asthma, cystic fibrosis, allergic rhinitis, chronic sinusitis and so on. Understanding the expression level and regulation mechanism of TMEM16A in different airway diseases and revealing its physiological function and pathological mechanism is critical for targeted disease treatment. This paper summarizes the research status of the discovery process, structural characteristics and regulatory mechanism of TMEM16A, and then summarizes the expression level of TMEM16A in asthma, cystic fibrosis, allergic rhinitis and chronic sinusitis ant related pathological mechanisms, clarifies the potential value of TMEM16A as a therapeutic target for the above four diseases, in order to guide treatment of airway inflammatory diseases.
Humans ; Asthma/metabolism* ; Anoctamin-1 ; Cystic Fibrosis/metabolism* ; Neoplasm Proteins/metabolism* ; Sinusitis/metabolism* ; Chloride Channels/metabolism* ; Rhinitis, Allergic/metabolism* ; Inflammation

OBJECTIVES: To propose a new method for optimizing radiotherapy planning for lung cancer by incorporating prognostic models that take into account individual patient information and assess the feasibility of treatment planning optimization directly guided by minimizing the predicted prognostic risk. METHODS: A mixed fluence map optimization objective was constructed, incorporating the outcome-based objective and the physical dose constraints. The outcome-based objective function was constructed as an equally weighted summation of prognostic prediction models for local control failure, radiation-induced cardiac toxicity, and radiation pneumonitis considering clinical risk factors. These models were derived using Cox regression analysis or Logistic regression. The primary goal was to minimize the outcome-based objective with the physical dose constraints recommended by the clinical guidelines. The efficacy of the proposed method for optimizing treatment plans was tested in 15 cases of non-small cell lung cancer in comparison with the conventional dose-based optimization method (clinical plan), and the dosimetric indicators and predicted prognostic outcomes were compared between different plans. RESULTS: In terms of the dosemetric indicators, D_95% of the planning target volume obtained using the proposed method was basically consistent with that of the clinical plan (100.33% vs 102.57%, P=0.056), and the average dose of the heart and lungs was significantly decreased from 9.83 Gy and 9.50 Gy to 7.02 Gy (t=4.537, P<0.05) and 8.40 Gy (t=4.104, P<0.05), respectively. The predicted probability of local control failure was similar between the proposed plan and the clinical plan (60.05% vs 59.66%), while the probability of radiation-induced cardiac toxicity was reduced by 1.41% in the proposed plan. CONCLUSIONS The proposed optimization method based on a mixed objective function of outcome prediction and physical dose provides effective protection against normal tissue exposure to improve the outcomes of lung cancer patients following radiotherapy.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods* ; Prognosis ; Radiotherapy, Intensity-Modulated/methods* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Radiotherapy Dosage ; Female ; Male ; Middle Aged

OBJECTIVES: To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. METHODS: The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. RESULTS: Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. CONCLUSIONS Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Animals ; Lipid Metabolism/drug effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mice, Nude ; Down-Regulation ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha/metabolism* ; Signal Transduction/drug effects* ; A549 Cells